Development of Chitosan-Coated Liposomes for Oral Delivery of Nadolol: Preparation, Characterization, and in vitro Permeability Studies.

INTRODUCTION

This study aims to enhance the oral bioavailability of Nadolol (NDL), a β-blocker used in the management of hypertension, by incorporating it into a liposome-based delivery system. To improve the formulation's stability, mucoadhesion, and permeability, chitosan coating was applied.

METHODS

Liposomes were prepared via the ethanol injection method using soy phosphatidylcholine and diacetyl phosphate. Chitosan coating was applied by adding chitosan solution (1% v/v acetic acid) at different chitosan-to-lipid ratios (0.1-0.4 w/w). The optimal formulation was selected based on particle size, PDI, and zeta potential. Characterization included encapsulation efficiency, drug loading, enzymatic stability, drug release, and Caco-2-based cytotoxicity and permeability assays.

RESULTS

The particle size and polydispersity index of the optimized formulations, L1-NDL, L2-NDL, L1C-NDL, and L2C-NDL, were measured as 27.02 ± 0.18 nm, 24.55 ± 0.22 nm, 160.10 ± 3.17 nm, 161.00 ± 2.30 nm, 0.39 ± 0.01, 0.37 ± 0.01, 0.19 ± 0.01, and 0.18 ± 0.02. Encapsulation efficiencies of 56.01 ± 3.70% and 43.87 ± 1.24% were recorded for L1C-NDL and L2C-NDL, respectively, while drug loading capacities were 61.47 ± 2.03% and 67.80 ± 0.74%, respectively. In an enzymatic degradation study, it was found that chitosan coating increased the stability of liposomes in the gastric media. The in vitro release was higher at both pH 1.2 and 6.8. Caco-2 assays confirmed >95% cell viability and enhanced permeability in the apical-tobasolateral direction. In the permeability study, chitosan-coated liposomal formulations demonstrated enhanced transport in the apical-to-basolateral direction, indicating improved intestinal permeability.

CONCLUSION

Chitosan-coated liposomes improved NDL's stability and permeability, showing promise as an effective oral delivery system.